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Annual Review of Nutrition

Volume 34, 2014

Hypoxia and Adipocyte Physiology: Implications for Adipose Tissue Dysfunction in Obesity

Abstract

Hypoxia develops in white adipose tissue in obese mice, resulting in changes in adipocyte function that may underpin the dysregulation that leads to obesity-associated disorders. Whether hypoxia occurs in adipose tissue in human obesity is unclear, with recent studies contradicting earlier reports that this was the case. Adipocytes, both murine and human, exhibit extensive functional changes in culture in response to hypoxia, which alters the expression of up to 1,300 genes. These include genes encoding key adipokines such as leptin, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2), which are upregulated, and adiponectin, which is downregulated. Hypoxia also inhibits the expression of genes linked to oxidative metabolism while stimulating the expression of genes associated with glycolysis. Glucose uptake and lactate release by adipocytes are both stimulated by hypoxia, and insulin sensitivity falls. Preadipocytes and macrophages in adipose tissue also respond to hypoxia. The hypoxia-signaling pathway may provide a new target for the treatment of obesity-associated disorders.

Keyword(s): brown fat, inflammation, leptin, oxygen, vascularization, white fat
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2014-07-17
2024-04-19
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Literature Cited

  1. Ahmed K, Tunaru S, Tang C, Müller M, Gille A. 1.  et al. 2010. An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metab. 11:311–19 [Google Scholar]
  2. Arch JRS, Ainsworth AT, Cawthorne MA, Piercy V, Sennitti MV. 2.  et al. 1984. Atypical β-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature 309:163–65 [Google Scholar]
  3. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K. 3.  et al. 1999. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. 257:79–83 [Google Scholar]
  4. Arunabh S, Pollack S, Yeh J, Aloia JF. 4.  2003. Body fat content and 25-hydroxyvitamin D levels in healthy women. J. Clin. Endocrinol. Metab. 88:157–61 [Google Scholar]
  5. Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M. 5.  et al. 2010. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am. J. Physiol. Endocrinol. Metab. 298:E1244–53 [Google Scholar]
  6. Bassi M, do Carmo JM, Hall JE, da Silva AA. 6.  2012. Chronic effects of centrally administered adiponectin on appetite, metabolism and blood pressure regulation in normotensive and hypertensive rats. Peptides 37:1–5 [Google Scholar]
  7. Bell-Parikh LC, Ide T, Lawson JA, McNamara P, Reilly M. 7.  et al. 2003. Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ. J. Clin. Invest. 112:945–55 [Google Scholar]
  8. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. 8.  2001. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat. Med. 7:947–53 [Google Scholar]
  9. Bjorneboe A, Bjorneboe GE, Drevon CA. 9.  1990. Absorption, transport and distribution of vitamin E. J. Nutr. 120:233–42 [Google Scholar]
  10. Blaak EE, van Baak MA, Kemerink GJ, Pakbiers MT, Heidendal GA. 10.  et al. 1995. β-adrenergic stimulation and abdominal subcutaneous fat blood flow in lean, obese, and reduced-obese subjects. Metabolism 44:183–87 [Google Scholar]
  11. Blomhoff R, Green MH, Berg T, Norum KR. 11.  1990. Transport and storage of vitamin A. Science 250:399–404 [Google Scholar]
  12. Blüher M. 12.  2009. Adipose tissue dysfunction in obesity. Exp. Clin. Endocrinol. Diabetes 117:241–50 [Google Scholar]
  13. Bouloumié A, Drexler HCA, Lafontan M, Busse R. 13.  1998. Leptin, the product of Ob gene, promotes angiogenesis. Circul. Res. 83:1059–66 [Google Scholar]
  14. Brahimi-Horn C, Pouysségur J. 14.  2007. Hypoxia in cancer cell metabolism and pH regulation. Essays Biochem. 43:165–78 [Google Scholar]
  15. Brahimi-Horn MC, Pouysségur J. 15.  2007. Oxygen, a source of life and stress. FEBS Lett. 581:3582–91 [Google Scholar]
  16. Braun RD, Lanzen JL, Snyder SA, Dewhirst MW. 16.  2001. Comparison of tumor and normal tissue oxygen tension measurements using OxyLite or microelectrodes in rodents. Am. J. Physiol. Heart Circul. Physiol. 280:H2533–44 [Google Scholar]
  17. Campfield LA, Smith FJ, Guisez Y, De Vos R, Burn P. 17.  1995. Recombinant mouse ob protein—evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546–49 [Google Scholar]
  18. Cannon B, Nedergaard J. 18.  2004. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84:277–359 [Google Scholar]
  19. Carrière A, Carmona M-C, Fernandez Y, Rigoulet M, Wenger RH. 19.  et al. 2004. Mitochondrial reactive oxygen species control the transcription factor CHOP-10/GADD153 and adipocyte differentiation: a mechanism for hypoxia-dependent effect. J. Biol. Chem. 279:40462–69 [Google Scholar]
  20. Chen B, Lam KSL, Wang Y, Wu D, Lam MC. 20.  et al. 2006. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes. Biochem. Biophys. Res. Commun. 341:549–56 [Google Scholar]
  21. Ching S, Kashinkunti S, Niehaus MD, Zinser GM. 21.  2011. Mammary adipocytes bioactivate 25-hydroxyvitamin D and signal via vitamin D receptor, modulating mammary epithelial cell growth. J. Cell Biochem. 112:3393–405 [Google Scholar]
  22. Choi CS, Kim YB, Lee FN, Zabolotny JM, Kahn BB. 22.  et al. 2002. Lactate induces insulin resistance in skeletal muscle by suppressing glycolysis and impairing insulin signaling. Am. J. Physiol. Endocrinol. Metab. 283:E233–40 [Google Scholar]
  23. Choi S, Cho K, Kim J, Yea K, Park G. 23.  et al. 2009. Comparative proteome analysis using amine-reactive isobaric tagging reagents coupled with 2D LC/MS/MS in 3T3-L1 adipocytes following hypoxia or normoxia. Biochem. Biophys. Res. Commun. 383:135–40 [Google Scholar]
  24. Cinti S. 24.  2001. The adipose organ: morphological perspectives of adipose tissues. Proc. Nutr. Soc. 60:319–28 [Google Scholar]
  25. Cinti S. 25.  2005. The adipose organ. Prostagl. Leuk. Essent. Fatty Acids 73:9–15 [Google Scholar]
  26. Cinti S. 26.  2009. Reversible physiological transdifferentiation in the adipose organ. Proc. Nutr. Soc. 68:340–49 [Google Scholar]
  27. Cinti S. 27.  2009. Transdifferentiation properties of adipocytes in the adipose organ. Am. J. Physiol. Endocrinol. Metab. 297:E977–86 [Google Scholar]
  28. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E. 28.  et al. 2005. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 46:2347–55 [Google Scholar]
  29. Clària J, Nguyen BT, Madenci AL, Ozaki CK, Serhan CN. 29.  2013. Diversity of lipid mediators in human adipose tissue depots. Am. J. Physiol. Cell Physiol. 304:C1141–49 [Google Scholar]
  30. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW. 30.  et al. 1996. Serum immunoreactive leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334:292–95 [Google Scholar]
  31. Cook KS, Min HY, Johnson D, Chaplinsky RJ, Flier JS. 31.  et al. 1987. Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science 237:402–5 [Google Scholar]
  32. Cummins EP, Taylor CT. 32.  2005. Hypoxia-responsive transcription factors. Pflügers Arch. 450:363–71 [Google Scholar]
  33. Cypess AM, Lehman S, Williams G, Tal I, Rodman D. 33.  et al. 2009. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360:1509–17 [Google Scholar]
  34. Dahlman I, Elsen M, Tennagels N, Korn M, Brockmann B. 34.  et al. 2012. Functional annotation of the human fat cell secretome. Arch. Physiol. Biochem. 118:84–91 [Google Scholar]
  35. de Oliveira EM, Sandri S, Knebel FH, Contesini CG, Campa A. 35.  et al. 2013. Hypoxia increases serum amyloid A3 (SAA3) in differentiated 3T3-L1 adipocytes. Inflammation 36:1107–10 [Google Scholar]
  36. Di Girolamo M, Newby FD, Lovejoy J. 36.  1992. Lactate production in adipose tissue: a regulated function with extra-adipose implications. FASEB J. 6:2405–12 [Google Scholar]
  37. Di Girolamo M, Skinner NS Jr, Hanley HG, Sachs RG. 37.  1971. Relationship of adipose tissue blood flow to fat cell size and number. Am. J. Physiol. 220:932–37 [Google Scholar]
  38. Ding C, Gao D, Wilding J, Trayhurn P, Bing C. 38.  2012. Vitamin D signalling in adipose tissue. Br. J. Nutr. 108:1915–23 [Google Scholar]
  39. Do MS, Nam SY, Hong SE, Kim KW, Duncan JS. 39.  et al. 2002. Metallothionein gene expression in human adipose tissue from lean and obese subjects. Horm. Metab. Res. 34:348–51 [Google Scholar]
  40. Doherty JR, Cleveland JL. 40.  2013. Targeting lactate metabolism for cancer therapeutics. J. Clin. Invest. 123:3685–92 [Google Scholar]
  41. Eckardt K, Sell H, Taube A, Koenen M, Platzbecker B. 41.  et al. 2009. Cannabinoid type 1 receptors in human skeletal muscle cells participate in the negative crosstalk between fat and muscle. Diabetologia 52:664–74 [Google Scholar]
  42. Emilsson V, Liu YL, Cawthorne MA, Morton NM, Davenport M. 42.  1997. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 46:313–16 [Google Scholar]
  43. Erecinska M, Silver IA. 43.  2001. Tissue oxygen tension and brain sensitivity to hypoxia. Respir. Physiol. 128:263–76 [Google Scholar]
  44. Fain JN, Kanu A, Bahouth SW, Cowan GS Jr, Hiler ML. 44.  et al. 2002. Comparison of PGE2, prostacyclin and leptin release by human adipocytes versus explants of adipose tissue in primary culture. Prostagl. Leukot. Essent. Fatty Acids 67:467–73 [Google Scholar]
  45. Famulla S, Horrighs A, Cramer A, Sell H, Eckel J. 45.  2011. Hypoxia reduces the response of human adipocytes towards TNFα resulting in reduced NF-κB signaling and MCP-1 secretion. Int. J. Obes. 36:986–92 [Google Scholar]
  46. Flores M. 46.  2005. A role of vitamin D in low-intensity chronic inflammation and insulin resistance in type 2 diabetes mellitus?. Nutr. Res. Rev. 18:175–82 [Google Scholar]
  47. Folkman J, Hahnfeldt P, Hlatky L. 47.  2000. Cancer: looking outside the genome. Nat. Rev. Mol. Cell Biol. 1:76–79 [Google Scholar]
  48. Foster DO, Frydman ML. 48.  1978. Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline. Can. J. Physiol. Pharmacol. 56:110–22 [Google Scholar]
  49. Foster DO, Frydman ML. 49.  1979. Tissue distribution of cold-induced thermogenesis in conscious warm- or cold-acclimated rats re-evaluated from changes in tissue blood flow: the dominant role of brown adipose tissue in the replacement of shivering by non-shivering thermogenesis. Can. J. Physiol. Pharmacol. 57:257–70 [Google Scholar]
  50. Frayn KN, Karpe F, Fielding BA, Macdonald IA, Coppack SW. 50.  2003. Integrative physiology of human adipose tissue. Int. J. Obes. 27:875–88 [Google Scholar]
  51. Frühbeck G, Gómez-Ambrosi J, Muruzabal FJ, Burrell MA. 51.  2001. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am. J. Physiol. Endocrinol. Metab. 280:E827–47 [Google Scholar]
  52. Fujisaka S, Usui I, Ikutani M, Aminuddin A, Takikawa A. 52.  et al. 2013. Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1α-dependent and HIF-1α-independent manner in obese mice. Diabetologia 56:1403–12 [Google Scholar]
  53. Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV. 53.  et al. 2007. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129:111–22 [Google Scholar]
  54. Gatenby RA, Gillies RJ. 54.  2004. Why do cancers have high aerobic glycolysis?. Nat. Rev. Cancer 4:891–99 [Google Scholar]
  55. Geiger G, Leiherer A, Muendlein A, Stark N, Geller-Rhomberg S. 55.  et al. 2011. Identification of hypoxia-induced genes in human SGBS adipocytes by microarray analysis. PLoS ONE 6:e26465 [Google Scholar]
  56. Glassford AJ, Yue P, Sheikh AY, Chun HJ, Zarafshar S. 56.  et al. 2007. HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes. Am. J. Physiol. Endocrinol. Metab. 293:E1590–96 [Google Scholar]
  57. Gonthier M-P, Hoareau L, Festy F, Matias I, Valenti M. 57.  et al. 2007. Identification of endocannabinoids and related compounds in human fat cells. Obesity 15:837–45 [Google Scholar]
  58. González-Muniesa P, de Oliveira CJ, Pérez de Heredia F, Thompson MP, Trayhurn P. 58.  2011. Fatty acids and hypoxia stimulate the expression and secretion of the adipokine ANGPTL4 (angiopoietin-like protein 4/fasting-induced adipose factor) by human adipocytes. J. Nutrigenet. Nutrigenom. 4:146–53 [Google Scholar]
  59. Goossens GH, Bizzarri A, Venteclef N, Essers Y, Cleutjens JP. 59.  et al. 2011. Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation 124:67–76 [Google Scholar]
  60. Gregor MF, Hotamisligil GS. 60.  2007. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J. Lipid Res. 48:1905–14 [Google Scholar]
  61. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT. 61.  et al. 1995. Weight-reducing effects of the plasma-protein encoded by the obese gene. Science 269:543–46 [Google Scholar]
  62. Halberg N, Khan T, Trujillo ME, Wernstedt-Asterholm I, Attie AD. 62.  et al. 2009. Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol. Cell. Biol. 29:4467–83 [Google Scholar]
  63. Hales CN, Luzio JP, Siddle K. 63.  1978. Hormonal control of adipose tissue lipolysis. Biochem. Soc. Trans. 43:97–135 [Google Scholar]
  64. Halestrap A, Meredith D. 64.  2004. The SLC16 gene family—from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflügers Arch. 447:619–28 [Google Scholar]
  65. Halestrap AP, Wilson MC. 65.  2012. The monocarboxylate transporter family—role and regulation. IUBMB Life 64:109–19 [Google Scholar]
  66. Hansen JB, Jorgensen C, Petersen RK, Hallenborg P, De Matteis R. 66.  et al. 2004. Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation. Proc. Natl. Acad. Sci. USA 101:4112–17 [Google Scholar]
  67. Harris RB. 67.  2000. Leptin—much more than a satiety signal. Annu. Rev. Nutr. 20:45–75 [Google Scholar]
  68. Hausman GJ. 68.  1985. The comparative anatomy of adipose tissue. New Perspectives in Adipose Tissue: Structure, Function and Development A Cryer, RLR Van 1–21 London: Butterworths [Google Scholar]
  69. Henegar C, Tordjman J, Achard V, Lacasa D, Cremer I. 69.  et al. 2008. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol. 9:R14 [Google Scholar]
  70. Himms-Hagen J. 70.  1985. Brown adipose tissue metabolism and thermogenesis. Annu. Rev. Nutr. 5:69–94 [Google Scholar]
  71. Himms-Hagen J. 71.  1989. Brown adipose tissue thermogenesis and obesity. Prog. Lipid Res. 28:67–115 [Google Scholar]
  72. Himms-Hagen J. 72.  1991. Neural control of brown adipose tissue thermogenesis, hypertrophy, and atrophy. Front. Neuroendocrinol. 12:38–93 [Google Scholar]
  73. Himms-Hagen J. 73.  1990. Brown adipose tissue thermogenesis—interdisciplinary studies. FASEB J. 4:2890–98 [Google Scholar]
  74. Hodson L, Humphreys SM, Karpe F, Frayn KN. 74.  2013. Metabolic signatures of human adipose tissue hypoxia in obesity. Diabetes 62:1417–25 [Google Scholar]
  75. Hoggard N, Hunter L, Duncan JS, Williams LM, Trayhurn P. 75.  et al. 1997. Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta. Proc. Natl. Acad. Sci. USA 94:11073–78 [Google Scholar]
  76. Höpfl G, Ogunshola O, Gassmann M. 76.  2004. HIFs and tumors—causes and consequences. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286:R608–23 [Google Scholar]
  77. Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S. 77.  et al. 2007. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56:901–11 [Google Scholar]
  78. Hotamisligil GS. 78.  2000. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int. J. Obes. 24:Suppl. 3S23–27 [Google Scholar]
  79. Hotamisligil GS. 79.  2006. Inflammation and metabolic disorders. Nature 444:860–67 [Google Scholar]
  80. Hotamisligil GS, Shargill NS, Spiegelman BM. 80.  1993. Adipose expression of tumor necrosis factor-α—direct role in obesity-linked insulin resistance. Science 259:87–91 [Google Scholar]
  81. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M. 81.  et al. 2000. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscl. Thromb. Vasc. Biol. 20:1595–99 [Google Scholar]
  82. Houstis N, Rosen ED, Lander ES. 82.  2006. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–48 [Google Scholar]
  83. Imtiyaz HZ, Williams EP, Hickey MM, Patel SA, Durham AC. 83.  et al. 2010. Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation. J. Clin. Invest. 120:2699–714 [Google Scholar]
  84. Ivan M, Kondo K, Yang H, Kim W, Valiando J. 84.  et al. 2001. HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464–68 [Google Scholar]
  85. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J. 85.  et al. 2001. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468–72 [Google Scholar]
  86. Jang M-K, Son Y, Jung MH. 86.  2013. ATF3 plays a role in adipocyte hypoxia-mediated mitochondria dysfunction in obesity. Biochem. Biophys. Res. Commun. 431:421–27 [Google Scholar]
  87. Jansson PA, Larsson A, Lonnroth PN. 87.  1998. Relationship between blood pressure, metabolic variables and blood flow in obese subjects with or without non-insulin-dependent diabetes mellitus. Eur. J. Clin. Invest. 28:813–18 [Google Scholar]
  88. Kabon B, Nagele A, Reddy D, Eagon C, Fleshman JW. 88.  et al. 2004. Obesity decreases perioperative tissue oxygenation. Anesthesiology 100:274–80 [Google Scholar]
  89. Karpe F, Fielding BA, Ilic V, Macdonald IA, Summers LKM. 89.  et al. 2002. Impaired postprandial adipose tissue blood flow response is related to aspects of insulin sensitivity. Diabetes 51:2467–73 [Google Scholar]
  90. Kemp PJ, Peers C. 90.  2007. Oxygen sensing by ion channels. Essays Biochem. 43:77–90 [Google Scholar]
  91. Kenneth NS, Rocha S. 91.  2008. Regulation of gene expression by hypoxia. Biochem. J. 414:19–29 [Google Scholar]
  92. Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M. 92.  et al. 2009. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29:1575–91 [Google Scholar]
  93. Kim KH, Song MJ, Chung J, Park H, Kim JB. 93.  2005. Hypoxia inhibits adipocyte differentiation in a HDAC-independent manner. Biochem. Biophys. Res. Commun. 333:1178–84 [Google Scholar]
  94. Kim SY, Choi YJ, Joung SM, Lee BH, Jung Y-S. 94.  et al. 2010. Hypoxic stress up-regulates the expression of Toll-like receptor 4 in macrophages via hypoxia-inducible factor. Immunology 129:516–24 [Google Scholar]
  95. Kim SY, Jeong E, Joung SM, Lee JY. 95.  2012. PI3K/Akt contributes to increased expression of Toll-like receptor 4 in macrophages exposed to hypoxic stress. Biochem. Biophys. Res. Commun. 419:466–71 [Google Scholar]
  96. Kopelman PG. 96.  2000. Obesity as a medical problem. Nature 404:635–43 [Google Scholar]
  97. Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A. 97.  et al. 2002. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2α. Mol. Cell. Biol. 22:7405–16 [Google Scholar]
  98. Lean MEJ, James WPT. 98.  1983. Uncoupling protein in human brown adipose tissue mitochondria: isolation and detection by specific antiserum. FEBS Lett. 163:235–40 [Google Scholar]
  99. Lean MEJ, James WPT, Jennings G, Trayhurn P. 99.  1986. Brown adipose tissue uncoupling protein content in human infants, children and adults. Clin. Sci. 71:291–97 [Google Scholar]
  100. Lee KY, Gesta S, Boucher J, Wang XL, Kahn CR. 100.  2011. The differential role of HIF1β/Arnt and the hypoxic response in adipose function, fibrosis, and inflammation. Cell Metab 14:491–503 [Google Scholar]
  101. Lewis JS, Lee JA, Underwood JC, Harris AL, Lewis CE. 101.  1999. Macrophage responses to hypoxia: relevance to disease mechanisms. J. Leukoc. Biol. 66:889–900 [Google Scholar]
  102. Li J, Byrne ME, Chang E, Jiang Y, Donkin SS. 102.  et al. 2008. 1α,25-Dihydroxyvitamin D hydroxylase in adipocytes. J. Steroid Biochem. Mol. Biol. 112:122–26 [Google Scholar]
  103. Lin Q, Lee Y-J, Yun Z. 103.  2006. Differentiation arrest by hypoxia. J. Biol. Chem. 281:30678–83 [Google Scholar]
  104. Liu C, Wu J, Zhu J, Kuei C, Yu J. 104.  et al. 2009. Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81. J. Biol. Chem. 284:2811–22 [Google Scholar]
  105. Liu J, Divoux A, Sun J, Zhang J, Clément K. 105.  et al. 2009. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat. Med. 15:940–45 [Google Scholar]
  106. Lolmède K, Durand de Saint Front V, Galitzky J, Lafontan M, Bouloumié A. 106.  2003. Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes. Int. J. Obes. 27:1187–95 [Google Scholar]
  107. Lopéz-Barneo J, Lopéz-Lopéz JR, Urena J, Gonzalez C. 107.  1988. Chemotransduction in the carotid body: K+ current modulated by pO2 in type I chemoreceptor cells. Science 241:580–82 [Google Scholar]
  108. Mack I, BelAiba RS, Djordjevic T, Gorlach A, Hauner H. 108.  et al. 2009. Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNFα exposure. Am. J. Physiol. Endocrinol. Metab. 297:E735–48 [Google Scholar]
  109. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y. 109.  et al. 1996. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). Biochem. Biophys. Res. Commun. 221:286–89 [Google Scholar]
  110. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH. 110.  et al. 1995. Leptin levels in human and rodent—measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med. 1:1155–61 [Google Scholar]
  111. Mariman EC, Wang P. 111.  2010. Adipocyte extracellular matrix composition, dynamics and role in obesity. Cell. Mol. Life Sci. 67:1277–92 [Google Scholar]
  112. Marin P, Rebuffé-Scrive M, Smith U, Björntorp P. 112.  1987. Glucose uptake in human adipose tissue. Metabolism 36:1154–60 [Google Scholar]
  113. Matsumoto S, Hyodo F, Subramanian S, Devasahayam N, Munasinghe J. 113.  et al. 2008. Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice. J. Clin. Invest. 118:1965–73 [Google Scholar]
  114. Mazzatti D, Lim F-L, O'Hara A, Wood IS, Trayhurn P. 114.  2012. A microarray analysis of the hypoxia-induced modulation of gene expression in human adipocytes. Arch. Physiol. Biochem. 118:112–20 [Google Scholar]
  115. Milner RE, Wang L, Trayhurn P. 115.  1989. Brown fat thermogenesis during hibernation and arousal in Richardson's ground squirrel. Am. J. Physiol. Reg. Integr. Comp. Physiol. 256:R42–48 [Google Scholar]
  116. Murdoch C, Muthana M, Lewis CE. 116.  2005. Hypoxia regulates macrophage functions in inflammation. J. Immunol. 175:6257–63 [Google Scholar]
  117. Nedergaard J, Bengtsson T, Cannon B. 117.  2007. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 293:E444–52 [Google Scholar]
  118. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J. 118.  et al. 2011. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480:104–8 [Google Scholar]
  119. Nicholls DG, Locke RM. 119.  1984. Thermogenic mechanisms in brown fat. Physiol. Rev. 64:1–64 [Google Scholar]
  120. O'Hara A, Lim F-L, Mazzatti D, Trayhurn P. 120.  2009. Microarray analysis identifies matrix metalloproteinases (MMPs) as key genes whose expression is up-regulated in human adipocytes by macrophage-conditioned medium. Pflügers Arch. 458:1103–14 [Google Scholar]
  121. O'Rourke RW, Meyer KA, Gaston G, White AE, Lumeng CN. 121.  et al. 2013. Hexosamine biosynthesis is a possible mechanism underlying hypoxia's effects on lipid metabolism in human adipocytes. PLoS ONE 8:e71165 [Google Scholar]
  122. O'Rourke RW, White AE, Metcalf MD, Olivas AS, Mitra P. 122.  et al. 2011. Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia 54:1480–90 [Google Scholar]
  123. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ. 123.  et al. 2006. Prevalence of overweight and obesity in the United States, 1999–2004. J. Am. Med. Assoc. 295:1549–55 [Google Scholar]
  124. Organ. World Health 2000. Obesity: preventing and managing the global epidemic. WHO Tech. Rep. Ser. #894. Geneva: World Health Organ. [Google Scholar]
  125. Ostlund RE, Yang JW, Klein S, Gingerich R. 125.  1996. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J. Clin. Endocrinol. Metab. 81:3909–13 [Google Scholar]
  126. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H. 126.  et al. 1999. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100:2473–76 [Google Scholar]
  127. Park Y-K, Park B, Lee S, Choi K, Moon Y. 127.  et al. 2013. Hypoxia-inducible factor-2α-dependent hypoxic induction of Wnt10b expression in adipogenic cells. J. Biol. Chem. 288:26311–22 [Google Scholar]
  128. Pasarica M, Gowronska-Kozak B, Burk D, Remedios I, Hymel D. 128.  et al. 2009. Adipose tissue collagen VI in obesity. J. Clin. Endocrinol. Metab. 94:5155–62 [Google Scholar]
  129. Pasarica M, Rood J, Ravussin E, Schwarz J-M, Smith SR. 129.  et al. 2010. Reduced oxygenation in human obese adipose tissue is associated with impaired insulin suppression of lipolysis. J. Clin. Endocrinol. Metab. 95:4052–55 [Google Scholar]
  130. Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT. 130.  et al. 2009. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58:718–25 [Google Scholar]
  131. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D. 131.  et al. 1995. Effects of the obese gene-product on body-weight regulation in ob/ob mice. Science 269:540–43 [Google Scholar]
  132. Penkowa M, Carrasco J, Giralt M, Molinero A, Hernandez J. 132.  et al. 2000. Altered central nervous system cytokine-growth factor expression profiles and angiogenesis in metallothionein-I+II deficient mice. J. Cereb. Blood Flow Metab. 20:1174–89 [Google Scholar]
  133. Pérez de Heredia F, Wood IS, Trayhurn P. 133.  2009. Acute and chronic hypoxia selectively modulates the expression of glucose transporters (GLUTs) in human adipocytes. Obes. Facts 2:Suppl. 239 [Google Scholar]
  134. Pérez de Heredia F, Wood IS, Trayhurn P. 134.  2010. Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Pflügers Arch. 459:509–18 [Google Scholar]
  135. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B. 135.  et al. 2010. Chronic peroxisome proliferator-activated receptor γ (PPARγ) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J. Biol. Chem. 285:7153–64 [Google Scholar]
  136. Plum LA, DeLuca HF. 136.  2010. Vitamin D, disease and therapeutic opportunities. Nat. Rev. Drug Discov. 9:941–55 [Google Scholar]
  137. Qi Y, Takahashi N, Hileman SM, Patel HR, Berg AH. 137.  et al. 2004. Adiponectin acts in the brain to decrease body weight. Nat. Med. 10:524–29 [Google Scholar]
  138. Quintero P, González-Muniesa P, Garcia-Diaz DF, Martinez JA. 138.  2012. Effects of hyperoxia exposure on metabolic markers and gene expression in 3T3-L1 adipocytes. J. Physiol. Biochem. 68:663–69 [Google Scholar]
  139. Rajala MW, Scherer PE. 139.  2003. The adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144:3765–73 [Google Scholar]
  140. Rausch ME, Weisberg SP, Vardhana P, Tortoriello DV. 140.  2008. Obesity in C57BL/6J mice is characterised by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int. J. Obes. 32:451–63 [Google Scholar]
  141. Regazzetti C, Peraldi P, Gremeaux T, Najem-Lendom R, Ben-Sahra I. 141.  et al. 2009. Hypoxia decreases insulin signaling pathways in adipocytes. Diabetes 58:95–103 [Google Scholar]
  142. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ. 142.  et al. 2004. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109:1292–98 [Google Scholar]
  143. Rennie KL, Jebb SA. 143.  2005. Prevalence of obesity in Great Britain. Obes. Rev. 6:11–12 [Google Scholar]
  144. Ricquier D, Bouillaud F. 144.  2000. Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance. J. Physiol. 529:3–10 [Google Scholar]
  145. Ricquier D, Néchad M, Mory G. 145.  1982. Ultrastructural and biochemical characterization of human brown adipose tissue in pheochromocytoma. J. Clin. Endocrinol. Metab. 54:803–7 [Google Scholar]
  146. Rocha S. 146.  2007. Gene regulation under low oxygen: holding your breath for transcription. Trends Biochem. Sci. 32:389–97 [Google Scholar]
  147. Rooney K, Trayhurn P. 147.  2011. Lactate and the GPR81 receptor in metabolic regulation: implications for adipose tissue function and fatty acid utilisation by muscle during exercise. Br. J. Nutr. 106:1310–16 [Google Scholar]
  148. Rosen ED, Spiegelman BM. 148.  2006. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444:847–53 [Google Scholar]
  149. Rosenow A, Noben JP, Bouwman FG, Mariman EC, Renes J. 149.  2013. Hypoxia-mimetic effects in the secretome of human preadipocytes and adipocytes. Biochim. Biophys. Acta 1834:2761–71 [Google Scholar]
  150. Rothwell NJ, Stock MJ. 150.  1979. A role for brown adipose tissue in diet-induced thermogenesis. Nature 281:31–35 [Google Scholar]
  151. Rothwell NJ, Stock MJ. 151.  1986. Brown adipose tissue. Recent Adv. Physiol. 10:349–82 [Google Scholar]
  152. Samuvel DJ, Sundararaj KP, Nareika A, Lopes-Virella MF, Huang Y. 152.  2009. Lactate boosts TLR4 signaling and NFκB pathway-mediated gene transcription in macrophages via monocarboxylate transporters and MD-2 up-regulation. J. Immunol. 182:2476–84 [Google Scholar]
  153. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. 153.  1995. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. 270:26746–49 [Google Scholar]
  154. Seale P, Bjork B, Yang W, Kajimura S, Chin S. 154.  et al. 2008. PRDM16 controls a brown fat/skeletal muscle switch. Nature 454:961–67 [Google Scholar]
  155. Seckl JR, Morton NM, Chapman KE, Walker BR. 155.  2004. Glucocorticoids and 11β-hydroxysteroid dehydrogenase in adipose tissue. Recent Prog. Horm. Res. 59:359–93 [Google Scholar]
  156. Segawa K, Fukuhara A, Hosogai N, Morita K, Okuno Y. 156.  et al. 2006. Visfatin in adipocytes is upregulated by hypoxia through HIF1α-dependent mechanism. Biochem. Biophys. Res. Commun. 349:875–82 [Google Scholar]
  157. Semenza GL. 157.  2003. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3:721–32 [Google Scholar]
  158. Semenza GL. 158.  2007. Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem. J. 405:1–9 [Google Scholar]
  159. Shin MK, Drager LF, Yao Q, Bevans-Fonti S, Yoo DY. 159.  et al. 2012. Metabolic consequences of high-fat diet are attenuated by suppression of HIF-1α. PLoS ONE 7:e46562 [Google Scholar]
  160. Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A. 160.  et al. 1998. Biological action of leptin as an angiogenic factor. Science 281:1683–86 [Google Scholar]
  161. Skurk T, Alberti-Huber C, Herder C, Hauner H. 161.  2007. Relationship between adipocyte size and adipokine expression and secretion. J. Clin. Endocrinol. Metab. 92:1023–33 [Google Scholar]
  162. Spencer M, Unal R, Zhu B, Rasouli N, McGehee RE Jr. 162.  et al. 2011. Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance. J. Clin. Endocrinol. Metab. 96:E1990–98 [Google Scholar]
  163. Sun K, Halberg N, Khan M, Magalang UJ, Scherer PE. 163.  2013. Selective inhibition of hypoxia-inducible factor 1α ameliorates adipose tissue dysfunction. Mol. Cell. Biol. 33:904–17 [Google Scholar]
  164. Sun K, Kusminski CM, Scherer PE. 164.  2011. Adipose tissue remodeling and obesity. J. Clin. Invest. 121:2094–101 [Google Scholar]
  165. Sun K, Tordjman J, Clement K, Scherer PE. 165.  2013. Fibrosis and adipose tissue dysfunction. Cell Metab. 18:470–77 [Google Scholar]
  166. Sun X, Zemel MB. 166.  2008. 1α, 25-Dihydroxyvitamin D and corticosteroid regulate adipocyte nuclear vitamin D receptor. Int. J. Obes. 32:1305–11 [Google Scholar]
  167. Tanji K, Irie Y, Uchida Y, Mori F, Satoh K. 167.  et al. 2003. Expression of metallothionein-III induced by hypoxia attenuates hypoxia-induced cell death in vitro. Brain Res. 976:125–29 [Google Scholar]
  168. Tedesco L, Valerio A, Dossena M, Cardile A, Ragni M. 168.  et al. 2010. Cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver. Diabetes 59:2826–36 [Google Scholar]
  169. Thurlby PL, Trayhurn P. 169.  1980. Regional blood flow in genetically obese (ob/ob) mice: the importance of brown adipose tissue to the reduced energy expenditure on non-shivering thermogenesis. Pflügers Arch. 385:193–201 [Google Scholar]
  170. Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T. 170.  et al. 2007. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc. Natl. Acad. Sci. USA 104:4401–6 [Google Scholar]
  171. Trayhurn P. 171.  1986. Brown adipose tissue and energy balance. Brown Adipose Tissue P Trayhurn, DG Nicholls 299–338 London: Edward Arnold [Google Scholar]
  172. Trayhurn P. 172.  2005. Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol. Scand. 184:285–93 [Google Scholar]
  173. Trayhurn P. 173.  2013. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol. Rev. 93:1–21 [Google Scholar]
  174. Trayhurn P, Ashwell M. 174.  1987. Control of white and brown adipose tissues by the autonomic nervous system. Proc. Nutr. Soc. 46:135–42 [Google Scholar]
  175. Trayhurn P, Beattie JH. 175.  2001. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc. Nutr. Soc. 60:329–39 [Google Scholar]
  176. Trayhurn P, Wang B, Wood IS. 176.  2008. Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?. Br. J. Nutr. 100:227–35 [Google Scholar]
  177. Trayhurn P, Wood IS. 177.  2004. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br. J. Nutr. 92:347–55 [Google Scholar]
  178. Trayhurn P, Wood IS. 178.  2005. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem. Soc. Trans. 33:1078–81 [Google Scholar]
  179. Tsushima Y, Nishizawa H, Tochino Y, Nakatsuji H, Sekimoto R. 179.  et al. 2013. Uric acid secretion from adipose tissue and its increase in obesity. J. Biol. Chem. 288:27138–49 [Google Scholar]
  180. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ. 180.  et al. 2009. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360:1500–8 [Google Scholar]
  181. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R. 181.  et al. 2009. Functional brown adipose tissue in healthy adults. N. Engl. J. Med. 360:1518–25 [Google Scholar]
  182. Virtanen KA, Lonnroth P, Parkkola R, Peltoniemi P, Asola M. 182.  et al. 2002. Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans. J. Clin. Endocrinol. Metab. 87:3902–10 [Google Scholar]
  183. Waldén TB, Hansen IR, Timmons JA, Cannon B, Nedergaard J. 183.  2012. Recruited versus nonrecruited molecular signatures of brown, “brite,” and white adipose tissues. Am. J. Physiol. Endocrinol. Metab. 302:E19–31 [Google Scholar]
  184. Wang B, Wood IS, Trayhurn P. 184.  2007. Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. Pflügers Arch. 455:479–92 [Google Scholar]
  185. Wang B, Wood IS, Trayhurn P. 185.  2008. Hypoxia induces leptin gene expression and secretion in human preadipocytes: differential effects of hypoxia on adipokine expression by preadipocytes. J. Endocrinol. 198:127–34 [Google Scholar]
  186. Wang B, Wood IS, Trayhurn P. 186.  2008. PCR arrays identify metallothionein-3 as a highly hypoxia-inducible gene in human adipocytes. Biochem. Biophys. Res. Commun. 368:88–93 [Google Scholar]
  187. Wang H, Eckel RH. 187.  2009. Lipoprotein lipase: from gene to obesity. Am. J. Physiol. Endocrinol. Metab. 297:E271–88 [Google Scholar]
  188. Wang Y, Wan C, Deng L, Liu X, Cao X. 188.  et al. 2007. The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal development. J. Clin. Invest. 117:1616–26 [Google Scholar]
  189. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL. 189.  et al. 2003. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112:1796–808 [Google Scholar]
  190. West DB, Prinz WA, Francendese AA, Greenwood MRC. 190.  1987. Adipocyte blood flow is decreased in obese Zucker rats. Am. J. Physiol. Reg. Integr. Comp. Physiol. 253:R228–33 [Google Scholar]
  191. Wong KE, Kong J, Zhang W, Szeto FL, Ye H. 191.  et al. 2011. Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice. J. Biol. Chem. 286:33804–10 [Google Scholar]
  192. Wood I, Stezhka T, Trayhurn P. 192.  2011. Modulation of adipokine production, glucose uptake and lactate release in human adipocytes by small changes in oxygen tension. Pflügers Arch. 462:469–77 [Google Scholar]
  193. Wood IS, Hunter L, Trayhurn P. 193.  2003. Expression of Class III facilitative glucose transporter genes (GLUT-10 and GLUT-12) in mouse and human adipose tissues. Biochem. Biophys. Res. Commun. 308:43–49 [Google Scholar]
  194. Wood IS, Pérez de Heredia F, Wang B, Trayhurn P. 194.  2009. Cellular hypoxia and adipose tissue dysfunction in obesity. Proc. Nutr. Soc. 68:370–77 [Google Scholar]
  195. Wood IS, Wang B, Lorente-Cebrian S, Trayhurn P. 195.  2007. Hypoxia increases expression of selective facilitative glucose transporters (GLUT) and 2-deoxy-D-glucose uptake in human adipocytes. Biochem. Biophys. Res. Commun. 361:468–73 [Google Scholar]
  196. Wood RJ. 196.  2008. Vitamin D and adipogenesis: new molecular insights. Nutr. Rev. 66:40–46 [Google Scholar]
  197. Wu J, Boström P, Sparks LM, Ye L, Choi JH. 197.  et al. 2012. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–76 [Google Scholar]
  198. Xu H, Barnes GT, Yang Q, Tan G, Yang D. 198.  et al. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112:1821–30 [Google Scholar]
  199. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N. 199.  et al. 2001. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7:941–46 [Google Scholar]
  200. Ye J, Gao Z, Yin J, He Q. 200.  2007. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am. J. Physiol. Endocrinol. Metab. 293:E1118–28 [Google Scholar]
  201. Yin J, Gao Z, He Q, Zhou D, Guo Z. 201.  et al. 2009. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am. J. Physiol. Endocrinol. Metab. 296:E333–42 [Google Scholar]
  202. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A. 202.  et al. 2000. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96:1723–32 [Google Scholar]
  203. Yu DY, Cringle SJ. 203.  2005. Retinal degeneration and local oxygen metabolism. Exp. Eye Res. 80:745–51 [Google Scholar]
  204. Yun Z, Maecker HL, Johnson RS, Giaccia AJ. 204.  2002. Inhibition of PPARγ2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia. Dev. Cell 2:331–41 [Google Scholar]
  205. Zbinden S, Wang J, Adenika R, Schmidt M, Tilan JU. 205.  et al. 2010. Metallothionein enhances angiogenesis and arteriogenesis by modulating smooth muscle cell and macrophage function. Arterioscler. Thromb. Vasc. Biol. 30:477–82 [Google Scholar]
  206. Zhang YY, Proenca R, Maffei M, Barone M, Leopold L. 206.  et al. 1994. Positional cloning of the mouse obese gene and its human homolog. Nature 372:425–32 [Google Scholar]
  207. Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A. 207.  et al. 2009. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 23:3113–20 [Google Scholar]
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Hypoxia and Adipocyte Physiology: Implications for Adipose Tissue Dysfunction in Obesity
Annual Review of Nutrition 34, 207 (2014); https://doi.org/10.1146/annurev-nutr-071812-161156
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